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PubMed1977

Cases of prolonged luteal activity in the non-pregnant dairy cow.

Regular measurements of progesterone in milk were made to monitor ovarian activity in over 300 commercial dairy cows from partiurition until pregnancy established. Six animals (approximately 1-5 per cent) which had not previously been inseminated showed prolonged luteal activity lasting for over 30 days. No apparent uterine abnormalities or infections were found in these cases. Prostaglandin analogue cloprostenol (Estrumate ICI) given intramuscularly induced complete luteolysis in treated animals. The subsequent fertility varied, but at least three of the six cows conceived again.

Animals↗
PubMed1976

The pharmacology of the pineal gland.

Only recently have a sufficient number of publications been available to legitimize a review of the pharmacology of the mammalian pineal organ. Two decades ago Kitay & Altschule reviewed the world literature on pineal physiology, which comprises several thousand papers, and concluded only that removal of the pineal, or administration of pineal extracts, somehow affected pigmentation in lower vertebrates and gonadal function in mammals (1). As the studies described below demonstrate, much more information is now available concerning the pharmacology of the pineal. This review subdivides present knowledge into two areas: (a) the effects on mammals of administering pineal extracts or pure synthetic or natural pineal constituents and (b) the effects of drugs and hormones on the pineal itself. As might be anticipated, the bulk of studies cited in both categories deals with the pineal hormone, melatonin. Melatonin was first isolated from bovine pineal extracts in 1958 by Lerner and his colleagues (2), who used as a marker the capacity of the hormone to aggregate the pigment granules in amphibian melanophores around the cell nucleus. Five years later, Wurtman et al (3) showed that melatonin affected a physiological function in mammals, that is, the size and secretion of the ovary, and subsequent studies have demonstrated that melatonin administration also modifies the growth, composition, and functional activities of numerous other organs. Only recently an assay was developed that allows quantification of the melatonin in human urine (4). The concentrations of the compound vary with a characteristic daily rhythm, peaking at night. The pineal's apparent role as the sole or major source of melatonin, the presence of melatonin in urine, and the demonstration that physiologic effects follow a pinealectomy or the administration of melatomin seem to justify labeling it a pineal hormone. Melatonin synthesis and pineal biosynthetic activity are generally controlled by the sympathetic nerves of this organ (5,6). Therefore, it should not be surprising that drugs known to modify the synthesis, release, or metabolism of norepinephrine in peripheral organs also affect pineal function. Melatonin is itself a derivative of another biogenic amine, serotonin, whose metabolism and actions are also affected by numerous drugs. Indeed, the pineal has often provided an apt tool for examining monoaminergic mechanisms for pharmacologists not specifically concerned with its particular functional properties.

Adenylyl Cyclases↗
PubMed1975

Blockage of progesterone-induced release of LH by intrabrain implants of actinomycin D.

Implants of cocoa butter (CB) or CB and actinomycin D (AD) were placed in the hypothalamus, amygdala, or anterior pituitary gland of testosterone-pretreated ovariectomized rats. The animals were then given an injection of 2.5 mg progesterone (P) at 11.00 h and sacriviced at approximately 16.30 h. Serum LH was determined by radioimmunoassay. Implants of AD placed in or near the arcuate nucleus and in other sites in the ventromedial hypothalamus blocked p-induced LH release, but those placed in the preoptic area or ventrolateral hypothalamus were only partially effective. Implants of AD in the amygdala or anterior pituitary gland had no detectable effect on LH release. Approximately 70 percent of the radioactivity in implants of 3H-AD diffused from the implant site within 8 h. of that recovered, most was found within 1 mm of the implant site. These results suggest that the ventromedial hypothalamus is one site at which AD acts to block P-induced LH release.

Amygdala↗
PubMed1976

Plasma norepinephrine during the rat estrous cycle and after progesterone treatment to the ovariectomized estrogen-primed rat.

In four-day cycling rats studied during the estrous cycle, the levels of circulating norepinephrine (NE) showed a sharp rise concomitant with the LH surge in the afternoon of proestrus. Following the peak, plasma NE fell rapidly to the minimum value by the morning of estrus. The administration of progesterone to ovariectomized estrogen-primed rats resulted in a surge in plasma NE levels 4 h after progesterone treatment. The maximal levels attained were 3-fold greater than baseline values, falling rapidly to reach basal values 8 h after the administration of progesterone. The amine levels remained unaffected 12-20 h later. The LH values attained a maximum 8 h after the injection of progesterone. In rats treated with estradiol benzoate (EB) followed by 0.1 ml of oil instead of progesterone, neither the NE nor the LH peak were observed. These findings are discussed with respect to the significance of increased amounts of plasma NE related to the LH surge.

Animals↗
PubMed1986

Effect of the variations of female sex hormones during the menstrual cycle upon serum somatomedin and growth-promoting activity.

Serum growth-promoting activity measured upon lymphocytes, sulfation activity and radioimmunoassayable somatomedin C (Sm-C) levels were measured in sera from women during the menstrual cycle. The data showed that: estradiol, progesterone, LH or FSH added in vitro do not increase the 3H-thymidine uptake into lymphocytes; the serum thymidine activity decreases during the luteal stage of the cycle, and is negatively correlated with the progesterone levels; the sulfation factor and Sm-C levels do not have significant variations during the menstrual cycle, and the GH maximum values are attained during the luteal stage.

Adult↗
PubMed1987

Airway responsiveness to methacholine during the natural menstrual cycle and the effect of oral contraceptives.

Exacerbations of symptoms have been reported in some women with asthma just prior to and during menstruation. We examined changes in airway responsiveness to methacholine during 2 consecutive menstrual cycles in 17 well-controlled asthmatics with a wide range of airway responsiveness. In 10 women with regular natural cycles, measurements were made 1 wk before and 1 wk after the start of menstruation to coincide with the highest and lowest progesterone levels. The mean concentration of methacholine to cause a fall in FEV1 of 20% (PC20) premenstruation was 1.49 mg/ml, which was not significantly different from the mean postmenstruation PC20 of 1.34 mg/ml (p = 0.45). Although there were only 10 subjects, the power was 96%, indicating little likelihood of any difference between the 2 phases. In 7 women taking oral contraceptives, the mean PC20, measured within 1 wk of completing a 21-day course, was 1.19 mg/ml, which was not different from the mean PC20 of 0.97 mg/ml measured after the start of menstruation but before restarting medication (p = 0.17). The power was 98%. In both groups, there was no difference in FEV1 or medication use during the cycle, but symptoms were worse during menstruation. The results suggest that the fluctuations in serum progesterone levels that occur during natural menstrual cycles are insufficient to alter airway responsiveness in an unselected sample of asthmatic women. They also demonstrate that changes in symptoms occur during the cycle both in women with natural cycles and those using contraceptives and that these changes are not related to serum progesterone levels or airway responsiveness.

Adult↗
PubMed1986

The circadian pattern of melatonin and its positive relationship with progesterone in women.

To investigate the possible role of melatonin in the regulation of the human menstrual cycle, the circadian pattern of melatonin was determined in the follicular and luteal phases of 10 normal women. Four-hourly sampling was used to derive a melatonin index which described the total exposure to melatonin for 24 h. This sampling procedure adequately represented the circadian melatonin output and demonstrated that pulses of melatonin secretion, inconsistent with a measured half-life of 47 min, did not exist. A significant increase (P less than 0.001) in the melatonin index was found in the luteal phase compared to that in the follicular phase. To investigate the influence of exogenous progestins on the melatonin pattern, repeated 24-h profiles were measured in 8 women taking the 3-phase contraceptive pill. There was a significant increase (P less than 0.01) in the melatonin index associated with an increase in the dose of progestin. These results are consistent with a positive relationship between melatonin and progesterone and suggest that changes in the circadian pattern of melatonin secretion, rising during the luteal phase with a fall before ovulation, may act as a modulator of cyclicity.

Administration, Intranasal↗
PubMed1987

Late luteal phase administration of RU486 for three successive cycles does not disrupt bleeding patterns or ovulation.

RU486, a 19-nor steroid, binds with high affinity to the receptors for progesterone and glucocorticoids, blocking the actions of these hormones on their target tissues. We conducted studies to determine whether RU486 administered at the end of the luteal phase would disturb the menstrual rhythm, ovulation, or hormonal parameters in the treatment and post-treatment cycles. The first study was done in six surgically sterilized women during two consecutive cycles. RU486 [17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-(1-propynyl)estra-4,9-dien-3-one; 100 mg/day] was given for 4 consecutive days, commencing on days 23-27 of the first cycle. Menstrual bleeding occurred by the second day of RU486 administration in all women and was indistinguishable from their usual bleeding pattern. The onset of this bleeding was advanced by RU486 administration, since it entailed shortening of the luteal phase with prolongation of the following follicular phase. Serum LH, FSH, estradiol, and progesterone levels were normal in five of the six women in both the treatment and posttreatment cycles. The second study was conducted in 10 women who were not exposed to the risk of pregnancy. RU486 (100 mg/day) was given for 4 consecutive days, commencing 4 days before their expected menses for 3 successive cycles, preceded and followed by 2 placebo-treated cycles. Bleeding patterns were indistinguishable during the RU486 and placebo cycles. Late luteal phase administration of RU486 consistently produced menstrual bleeding within 1-3 days of drug administration. Daily early morning urinary LH excretion in 6 women and estrone glucuronide and pregnanediol glucuronide excretion in 5 women during both placebo and RU486 cycles were consistent with luteinization, suggesting ovulation and appropriate corpus luteum function. We conclude that RU486 has no major effect on menstrual cycle events if given at the time of the natural progesterone withdrawal that occurs before menses in nonpregnant women.

Adult↗
PubMed1976

[Preovulatory changes of steroidogenesis in isolated rabbit follicles (author's transl)].

In an attempt to investigate the effect of ovulating hormone on the steroidogenesis of mature follicles in the course of ovulation, transitory changes of steroidogenesis in isolated rabbit follicles have been studied at several intervals after injection of an ovulatory dose of human chorionic gonadotropin (hCG). Five to ten follicles of approximately 1-2 mm in diameter were isolated from ovaries of a mature rabbit (2.5-3.0 kg) under streomicroscope, before and at the 3rd, 6th, 9th and 12th hours after intravenous injection of of 100 IU/kg of hCG. Follicles were incubated with 100 muCi of acetate-1-14C in 2 ml of Krebs-Ringer bicarbonate buffer (pH 7.4) at 37 degrees C for 3 hours under 95% oxygen plus 5% carbon dioxide. Each incubation was terminated by quick freezing and stored forzen at -20 degrees C until eighty follicles had been collected for each time period before commencement of analysis. Incorporation of radioactive acetate into pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone., 20 alpha-dihydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone and estradiol-17beta were analysed by the reverse dilution technique and identified in radiochemically pure form by recrystallization to constant specific activities. The steroidogenic activity of the follicles was evaluated by overall as well as fractionated incorporations. A peak in the overall incorporation of 14C- acetate into the ten steroids at the 3rd hour after hCG injection, followed by gradual decrease up to the 9th hour was observed. The incorporation decreased markedly to a minimum level at the 12th hour after hCG injection, which was below the level of preinjection control. Comparable quantitative fluctuations were found with the fractionated incorporation of 14C-acetate into the C21 and C18 steroids in the time sequence following hCG injection. However, the fractionated incorporation into C19 steroids reached to a maximum at the 6th hour after hCG injection. 5istribution patterns of incorporation among the individual steroids were varied at each interval of time. In the non-injected control, mature follicles synthesized predominantly estradiol-17beta, testosterone and androstenedione. Divergent steroids were formed from radioactive acetate at the 3rd hour after hCG injection. These included porgestogen, androgen and estrogen, but pregnenolone and 17hydroxyprogesterone were the two principal steroids produced. There was no essential difference in the steroidogenic patterns between the 6th and 9th hour, the major products being C21 and C19 steroids such as pregnenolone, 17hydroxyprogesterone, dehydroipiandrosterone and testosterone. The three androgens were the major steroids formed at the 12th hour after hCG injection. Thus the chages in the steroidogenic profile of the follicle was obvious in the course of ovulation. The basis of qualitative changes in follicular steroidogenesis during the process of ovulation have been discussed in connection with an accompanying effect of an ovulatory dose of hCG.

Acetates↗
PubMed1977

Examination of the role of FSH in periovulatory events in the hamster.

The need for endogenous FSH in the periovulatory events such as oocyte maturation, ovulation, luteinization, maintenance of luteal function and follicular maturation was examined in the cyclic hamster. A specific antiserum to ovine FSH, shown to be free of antibodies to LH and to cross-react with FSH of the hamster, was used to neutralize endogenous FHS at various times. Administration of this antiserum during pro-oestrus did not affect oocyte maturation and ovulation, as judged by the normality of the ova to undergo fertilization and normal implantation. It also had no effect on the process of luteinization or on the maintenance of luteal function as indicated by the normal levels of plasma and luteal progesterone during pro-oestrus and oestrus during the cycle and in pregnancy. All these processes were, however, disrupted by administration of an antiserum to ovine LH, thereby demonstrating their dependence on endogenous LH. Although FSH antiserum given at pro-oestrus did not prevent the imminent ovulation, it blocked the ovulation occurring at oestrus of the next cycle. This antiserum was effective in preventing the ensuing ovulation when given at any other time of the cycle until the morning of pro-oestrus. It is concluded that, in the hamster, high levels of FSH during pro-oestrus and oestrus are required for initiating maturation of a new set of follicles which are dependent on the trophic support of FSH throughout the cycle until the morning of pro-oestrus. Such follicles then appear to need only LH for subsequent ovulatory and associated processes.

Animals↗
PubMed1976

Plasma hormone concentrations during the menstrual cycle of normal Chinese women.

The concentrations of progesterone, estrogens, luteinizing hormone and follicle stimulating hormone were measured in samples of plasma taken frequently during normal menstrual cycles in fourteen Chinese women. Each of the menstrual cycles was characterized by hormonal changes which were comparable to those previously reported in Caucasian subject.

Adult↗